Androgen deprivation therapy is the core treatment for prostate cancer, but many patients progress to castration-resistant disease. This review examines four nuclear hormone receptors as additional targets, the androgen receptor (AR), thyroid hormone receptor β (TRβ), retinoic acid receptor γ (RARγ), and the vitamin D receptor (VDR). AR, TRβ, and RARγ antagonists can kill patient-derived cancer cells, including cancer stem-like cells, while largely sparing normal prostate epithelium. The VDR is the exception: its ligand 1,25D3 drives growth arrest and apoptosis in vitro, but clinical use has been limited by hypercalcaemia and resistance. The authors highlight crosstalk between these receptors, such as shared DNA binding sites and competition for RXR, and propose that mapping it could enable new combination therapies beyond androgen blockade.