When do you use que vs quien in Spanish?

Que is the default for both people and things in restrictive clauses (clauses that identify which one you mean): el hombre que vive aquí (the man who lives here), el libro que leí (the book that I read). Quien is reserved for people in non-restrictive clauses (the ones in commas adding extra information): mi padre, quien vive en Madrid, viene mañana (my father, who lives in Madrid, is coming tomorrow). After a preposition referring to a person, quien is also standard: la mujer con quien hablé (the woman I spoke with). For everyday use, que covers about 80% of cases.

What does lo que mean in Spanish?

Lo que means 'what' or 'that which' when there's no specific noun to refer back to - the antecedent is an idea, a situation, or something unidentified. No entiendo lo que dices (I don't understand what you're saying). Lo que me importa es la verdad (what matters to me is the truth). Use lo que when the thing being referred to is abstract or unidentified; use que or el que / la que when there's a specific noun in mind.

Spanish Relative Pronouns

A relative pronoun connects a noun to a clause that modifies it. The Spanish set is small.

que: the default

Que is the workhorse relative pronoun. It covers both people and things, in both restrictive and non-restrictive clauses, and it's invariable.

El libro que leí ayer es interesante. (The book that I read yesterday is interesting.)
La mujer que vive aquí es médica. (The woman who lives here is a doctor.)
Los amigos que tengo en Madrid son geniales. (The friends I have in Madrid are great.)
El coche que compré es nuevo. (The car that I bought is new.)

Note: English often drops the relative pronoun ("the book I read"), but Spanish never does. El libro leí is ungrammatical; you must include que.

Que works with prepositions for things and concepts:

El libro del que te hablé. (The book I told you about.)
La idea con la que estoy de acuerdo. (The idea I agree with.)

After most prepositions, que needs an article: del que, con el que, en el que, a la que.

quien / quienes: people in non-restrictive clauses

Quien (singular) and quienes (plural) refer to people in two specific contexts:

1. Non-restrictive clauses (the ones in commas, adding extra information):

Mi padre, quien vive en Madrid, viene mañana. (My father, who lives in Madrid, is coming tomorrow.)
María, quien es médica, trabaja en el hospital. (Maria, who is a doctor, works at the hospital.)

In restrictive clauses (no commas), que is the default even for people: el hombre que vive aquí, not "el hombre quien vive aquí".

2. After a preposition referring to a person:

La mujer con quien hablé es mi profesora. (The woman I spoke with is my teacher.)
Los amigos para quienes compré los regalos. (The friends I bought the gifts for.)
El hombre de quien te hablé. (The man I told you about.)

After a preposition, quien is preferred for people, where que would need the article (con la que, de quien).

lo que: "what" / "that which"

Lo que is the neuter relative pronoun for situations where there's no specific noun antecedent - the thing being referred back to is an idea, an action, a situation.

No entiendo lo que dices. (I don't understand what you're saying.)
Lo que me gusta es viajar. (What I like is travelling.)
Haz lo que quieras. (Do what you want.)
No sé lo que pasa. (I don't know what's happening.)

When there's a specific noun in mind, use que with the article instead:

No sé el libro que prefieres. (I don't know the book you prefer. - specific noun, libro)
No sé lo que prefieres. (I don't know what you prefer. - abstract)

donde and cuando as relatives

Donde (where) and cuando (when) can function as relative adverbs, linking a clause to a noun of place or time. No written accent in this use.

La casa donde vivo es pequeña. (The house where I live is small.)
El restaurante donde comimos ayer. (The restaurant where we ate yesterday.)
El año cuando me casé. (The year I got married.)
En aquellos tiempos cuando vivía en Madrid. (In those times when I lived in Madrid.)

These often interchange with en el que / en la que / en que:

La casa en la que vivo = la casa donde vivo
El año en que me casé = el año cuando me casé

Donde and cuando are simpler and more conversational; the en + article + que forms are slightly more formal.

Worked examples

El libro que estoy leyendo es muy bueno. (The book I'm reading is very good.)
La mujer que conocí ayer es muy simpática. (The woman I met yesterday is very nice.)
Mi hermano, quien vive en París, viene a verme. (My brother, who lives in Paris, is coming to see me.)
No sabía lo que querías decir. (I didn't know what you meant.)
La ciudad donde nací es muy pequeña. (The city where I was born is very small.)
El día cuando llegué a Madrid llovía. (The day I arrived in Madrid, it was raining.)
El profesor con quien estudio es muy bueno. (The teacher I study with is very good.)

Common mistakes English speakers make

Dropping the relative pronoun the way English does: el libro leí ayer is wrong, it's el libro que leí ayer. Spanish never drops the relative pronoun. Defaulting to quien for all people, including in restrictive clauses: la mujer quien vive aquí is wrong, it's la mujer que vive aquí. And using que instead of lo que when there's no specific noun antecedent: no entiendo que dices would mean "I don't understand that you're saying" (a different sentence); no entiendo lo que dices is the right form.