Despite the potentially vast T-cell repertoire, biased alphabeta T-cell receptor (TCR) usage has emerged as a common theme in immunity. Examples of TCR bias are observed in classical polymorphic major histocompatibility complex (MHC)-restricted immune responses as well as in T-cell responses to non-classical, monomorphic Ag-presenting molecules, such as CD1d. Recent data have implicated the structural landscape of these antigen-presenting molecules as one of the drivers of TCR bias. Here we review recent advances in the field, focussing on structural data pertaining to biased TCR usage, and discuss the implications for T-cell repertoire selection, MHC restriction and therapeutic development.