Phosphorus is an essential element for correct functioning of the organism. Alteration of serum phosphorus may be due to reduced dietary intake, altered by intra-extracellular, by excretion or reabsorption from the intestine, bone and kidney. In patients with chronic hepatitis B, hypophosphatemia may be secondary to several causes among which the most frequent are related to the use of drugs and the deficiency of vitamin D. Tenofovir is a first choice drug for the treatment of chronic hepatitis B and it can be used in patients with mild renal impairment. In fact renal failure induced by TDF is not frequent, dose-dependent and usually reversible. However, it’s recommended to avoid use other nephrotoxic drugs during treatment with TDF; monitor kidney function and phosphorus metabolism before and during therapy; adjust the doses of the drugs to the degree of renal failure; verify the presence of proximal tubulopathy through the calculation of the EFPi and the TMPi/GFR and consider the suspension of the TDF in the case of severe hypophosphoremia (< 1 mg / dl) or creatinine clearance < 50 ml/min). The aim of this review is to facilitate the recognition of druginduced hypophosphatemia and differentiate it from that due to other causes, in order to avoid unnecessary discontinuation of antiviral therapy.