Clinical observations have suggested that carnitine supplementation may be beneficial to a subset of patients receiving chronic hemodialysis. In the absence of definitive clinical trials, the clinician must decide for an individual patient whether a trial of carnitine therapy is justified. The institution of carnitine therapy is further complicated by the availability of oral and intravenous dosing forms and by the compound's complex pharmacokinetics. The oral systemic bioavailability of carnitine in normal subjects is 5% to 16%, with peak plasma carnitine concentrations reached 2 to 6 hours after dosing. Carnitine is initially distributed into extracellular water and then more slowly enters tissue compartments with complex kinetics. Elimination of carnitine is through the urine or dialysate. Intravenous carnitine administration results in large peak plasma concentrations and assures systemic bioavailability. Orally administered carnitine has been reported to have clinical efficacy in hemodialysis patients in doses of 2 to 4 g per day in divided doses. Intravenous carnitine has also been widely used in clinical trials in attempts to demonstrate efficacy in the hemodialysis population; however, the available data do not establish the superiority of the intravenous formulation over the oral form. Intravenous carnitine may have theoretical advantages in initiating treatment when high peak concentrations are required to facilitate carnitine reaching nonhepatic tissue sites or when oral carnitine therapy is not feasible due to poor tolerance or compliance. Although comparative trials are lacking, it is probable that oral therapy can be used for long-term maintenance, regardless of which formulation was used to initiate therapy. The decision to use carnitine therapy, as well as the dose and route of administration, requires individualization based on the clinical status of the patient and the goals of therapy.