Tenofovir disoproxil fumarate (TDF) is a nucleotide analog used as part of HIV therapy. Its favorable profile in terms of high efficacy, low toxicity and once-daily dosing makes TDF one of the most attractive antiretroviral agents, and therefore, it is widely used. However, cases of kidney tubular dysfunction have been reported and concern exists regarding the long term use of TDF. Owing to the high interindividual variability in the presentation of kidney function abnormalities, research has recently focused on host genetic factors predisposing to TDF-associated renal dysfunction. Transporter proteins involved in the renal elimination of TDF, such as organic anion transporter 1 or multidrug resistant protein 2 or 4, seem to be involved importantly and several genetic polymorphisms in these proteins have been associated with an increased risk of kidney tubulopathy in patients treated with TDF. In this review, all relevant pharmacogenetic factors that may play a role in the risk of renal toxicity associated with the use of tenofovir are summarized.