Steroid hormones are believed to enter cells solely by free diffusion through the plasma membrane. However, recent work on the uptake of 25-hydroxyvitamin D3 into the kidney has identified an endocytic pathway that is responsible for the delivery of this steroid to renal tissues. This finding led to a new perception that endocytosis may play an important role in the cell-type-specific targeting and uptake of steroid hormones. In the present review, we describe the molecular components (e.g. steroid carriers, endocytic receptors and intracellular transport proteins) that constitute this novel pathway for tissue-specific uptake of vitamin D metabolites.