Androgens, vital for male sexual development and behavior, function through the androgen receptor (AR), a transcription factor controlled by testosterone and 5α-dihydrotestosterone. AR’s action in mediating androgen sensitivity of gene expression involves, in addition to androgen-induced DNA/chromatin binding, interactions with other transcription factors and coregulators and posttranslational modifications. These interactions are crucial in modulating AR’s activity, playing significant roles in AR’s tissue-specific actions. Based on single-cell analyses, AR expression varies across testicular cell types, being high in Leydig cells, moderate in Sertoli cells and peritubular cells, and absent in germ cells. Testis cell–specific AR knockout studies have shown different impacts on fertility and testosterone levels, highlighting AR’s critical role in Leydig cell development and testosterone production. Structural alterations in AR, including polymorphisms and mutations, mutations particularly in the AR ligand-binding domain, can significantly affect androgen sensitivity and lead to androgen insensitivity syndrome (AIS). The mutations result in varying AIS severities, from complete to mild, impacting receptor concentration and functionality. The complexity of AIS is potentially increased by alterations in AR-interacting coregulators and tissue-specific transcription factors, as is the case with androgen sensitivity in general. Understanding these interactions is key to unraveling more detailed mechanisms of androgen sensitivity.