Although lymphoma is one of the few solid tumours for which chemotherapy can be curative, the treatment of refractory lymphoma remains a major clinical problem. P-glycoprotein (Pgp), the drug efflux pump encoded by the MDR-1 gene is associated with multidrug resistance in several laboratory models of drug resistance, and a number of investigators have attempted to establish a role for Pgp in refractory lymphoma. Despite a considerable variability in the results of these studies investigating Pgp expression in lymphoma, the preponderance of the data suggests that Pgp may at least in part account for drug resistance in this disease. Several clinical trials using Pgp modulating compounds have attempted to reverse the drug resistant phenotype of refractory lymphoma. These studies, although difficult to interpret because of the effect of Pgp modulators on chemotherapeutic drug pharmacokinetics, also suggest a role for Pgp in mediating drug resistance in a subset of patients with refractory lymphoma. Studies with newer Pgp modulating agents with phase III designs will be needed before Pgp modulation can be considered for incorporation into routine oncologic practice.