In the past decade, chromatin immunoprecipitation sequencing (ChIP-seq) has emerged as the dominant technique for those wishing to perform genome-wide protein:DNA profiling. Owing to the tissue- and cell-type-specific nature of epigenetic marks, the field has been driven towards obtaining data from ever-lower cell numbers. In this review, we focus on the methodological developments that have lowered input requirements and the biological findings they have enabled, as we strive towards the ultimate goal of robust single-cell ChIP-seq.