Zidovudine is the cornerstone of current antiretroviral treatment of human immunodeficiency virus (HIV) infection. Its use, however, frequently leads to adverse reactions, including myelosuppression. Zidovudine pharmacokinetics show large interindividual variation with indications of pharmacokinetic-pharmacodynamic relationships, but a clear therapeutic window has not yet been defined. Individualisation of zidovudine therapy with monitoring of drug concentrations might be desirable. This review considers (intracellular) monitoring of zidovudine and anabolites for individualisation of zidovudine therapy and the achievements in describing pharmacokinetic-pharmacodynamic relationships so far.