Drug-induced kidney disease occurs primarily in patients with underlying risk factors. A number of factors enhance the vulnerability of the kidney to the nephrotoxic effects of drugs and toxins. They are broadly categorized as patient-specific, kidney-related, and drug-related factors. One, two, or all three of the factor categories can act to promote various forms of renal injury. Importantly, all compartments of the kidney can be affected and result in one or more classic clinical renal syndromes. These include acute kidney injury, various tubulopathies, proteinuric renal disease, and chronic kidney disease. Recognizing risk factors that increase renal vulnerability to drug-induced kidney disease is the first step in reducing the renal complications of drugs and toxins.