In 2017 1.8 million people became newly infected with HIV and 940,000 people died from AIDS-related illnesses. The objective set by UNAIDS is to reduce new HIV infections to fewer than 500,000 by 2020 but usual prevention methods have not produced the desired results that would follow ambitious global targets. Therefore, there is a great need for additional improvements of combined prevention with new methods. One of these new methods is PrEP – pre-exposure prophylaxis of HIV infection with antiretroviral drugs. Randomized clinical trials demonstrated safety and efficacy of PrEP which exceeds 90%. The degree of adherence is the main determinant of efficacy. Currently the only drugs approved in this indication are 300 mg of tenofovir disoproxil fumarate (TDF) and 200 mg of emtricitabine (FTC) used as a combination. Depending on countries, PrEP can be used as 1 tablet taken on a daily basis (daily regimen) or as an on-demand drug taken before and after sexual intercourse (two tablets before the sexual intercourse, one tablet 24 and 48 hours after the first tablet). PrEP is recommended to all populations at major risk of HIV infection such as men who have sex with men (MSM), transgender women, people who inject drugs (PWID), female sex workers and men and women who have heterosexual contacts with partners of unknown HIV status or with detectable HIV viral load. Before prescribing PrEP it is important to rule out established or acute HIV infection to avoid resistance development. Clinician should determine renal function because creatinine clearance of ≤60 ml/min is a contraindication to PrEP use. Candidate should also be tested for hepatis B and C viruses and sexually transmitted infections (STI). Important follow-up procedures are an HIV test every 3 months, STI screening and adherence counselling. PrEP is safe, with no side-effects for majority of users. More common side-effects are transient gastrointestinal symptoms whereas reversable impairment of kidney function and bone density reduction are even less common. Despite heterogeneous results, the data depict high incidence rates of STIs among MSM using PrEP but in most cases there was no further increase in STI incidence rates during PrEP use (no risk compensation). By the end of 2018 at least 380,000 people have started to take PrEP but the global target of UNAIDS is 3 million people taking PrEP by 2020. Currently there are several ongoing clinical trials of new PrEP drugs and long-acting preparations such as cabotegravir and VRCO1 antibody.