Statins have shown high efficacy in managing hypercholesterolemia in patients requiring chronic drug treatment, particularly those who show comorbidity and thus receive concomitant medication for other pathologies. According to the reported data extensively reviewed in this work, absorption and elimination are the kinetic processes mainly affected by this type of interaction, while distribution and protein binding is only slightly modified. Products (drugs or food) with the ability to affect the activity of protein-mediated transport and/or P450 cytochrome systems, particularly the P-glycoprotein and/or CYP3A4, respectively, are expected to cause pharmacokinetic interactions with statins. The intensity of the interaction is dependent on the statin kinetic profile and the capacity of the coadministered product to alter the systems mentioned above. Modification of the total HMG-CoA inhibitors instead of just the parent drug profile is to be considered when evaluating the clinical relevance of the interaction. Interindividual variability must also be taken into account when extrapolating results from studies performed in small groups of relatively healthy individuals. Patients treated with other drugs that have the potential ability to interact with statins should be monitored.