Nitrofurantoin and nitroxoline are oral antibiotics for the treatment or prophylaxis of acute urinary tract infections. New interest in both these drugs is increasing because of the emergence of resistance to other antibiotics, but knowledge of their pharmacokinetics (PK) is lacking since they were developed before the advent of standardized research for drug approval. The aims of this review were to (i) summarize the PK data reported in the literature and (ii) to identify PK knowledge gaps. The current body of PK knowledge of both drugs appears to be poor and mainly based on old studies. Nitrofurantoin PK values were obtained from studies using many variables, e.g. formulations, crystal sizes and analytical methods, resulting in high interindividual variability in PK parameters and no uniform PK profile. Clinical experience and PK data for nitroxoline are even more limited since the drug is registered in only Germany and a few (Eastern European) countries. Clinical studies in relevant patient populations are needed with commercially available nitrofurantoin and nitroxoline formulations at approved dosing regimens to more fully characterize their PK profiles, and to investigate the influence of patient characteristics on these profiles in order to optimize efficacy and avoid toxicity and emergence of resistance. Only with this updated knowledge and efficacy data from well-structured trials can both drugs maintain their antimicrobial activity against uropathogens.