Considered more efficacious and safer than traditional systemic drugs, biologic therapies have dramatically improved the quality of life of patients with psoriasis. Recently, there has been a proliferation of new targeted treatment options, including anti-interleukin-17, anti-interleukin-12/23, as well as small-molecule drugs such as apremilast. There are nevertheless some concerns regarding their use, especially in patients with chronic infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV). It has been estimated that two billion individuals are infected with HBV worldwide and approximately 240 million have chronic HBV infection. Moreover, there are approximately 71 million individuals with chronic HCV infection worldwide, with a high percentage of them unaware of being infected. As patients with HBV and HCV infections are excluded from controlled clinical trials investigating new drugs, data regarding their safety in patients with psoriasis are based almost exclusively on case reports and small retrospective cohort studies and need to be constantly updated. The risk of HBV reactivation can be defined as: high risk (≥ 10%), moderate risk (1-10%), and low risk (< 1%) depending on the type of immunosuppressive therapy stratified by the presence or absence of hepatitis B surface antigen but positivity to anti-hepatitis B core antigen. Hepatitis B surface antigen-positive patients treated with tumor necrosis factor-α inhibitors, ustekinumab, or cyclosporine carry a high or moderate risk of HBV reactivation and should be considered candidates for prophylactic anti-HBV therapy. Once therapy is commenced, it is important to check HBV DNA levels every 3 months. Hepatitis B virus reactivation typically occurs with immune reconstitution and therefore antiviral therapy should continue for 6-12 months after stopping immunosuppression. Hepatitis B surface antigen-positive patients who are prescribed methotrexate, acitretin, or apremilast have a low risk and need to be monitored for viral reactivation by determining alanine aminotransferase and HBV DNA levels every 3 months. No conclusive data are available for interleukin-17 and interleukin-23 inhibitors. Anti-hepatitis B core antigen-positive patients treated with tumor necrosis factor-α inhibitors, ustekinumab, and cyclosporine are linked to a moderate risk of reactivation, and they should preferably undergo HBV DNA or hepatitis B surface antigen and alanine aminotransferase testing rather than be subjected to routine pre-emptive therapy. Anti-hepatitis B core antigen-positive patients receiving methotrexate, acitretin, or apremilast have a low risk of reactivation and do not require anti-HBV therapy, nor should monitoring be considered mandatory. No conclusive data are available for interleukin-17 and interleukin-23 inhibitors.