Always mention the write cost trade-off. Indexes speed up reads but slow down inserts and updates because the index must be maintained.
Strong answers explain B-tree structures conceptually, cover when indexes help (frequent WHERE/JOIN/ORDER BY columns, high cardinality), and when they hurt (write-heavy tables, low cardinality, small tables). Best candidates discuss composite indexes, covering indexes, and using EXPLAIN to verify query plans.
Fundamental backend knowledge. Mid-level developers should be comfortable here. Ask follow-up: "How do you decide which columns to include in a composite index?"