According to the Food and Drug Administration (FDA) reports, approximately 8 in 10 prescriptions filled in the United States are for generic medications, with an expectation that this number will increase over the next few years. The impetus for this emphasis on generics is the cost disparity between them and brand-name products. The use of FDA-approved generic drugs saved 158 billion dollars in 2010 alone. In the current health care climate, there is continually increasing pressure for prescribers to write for generic alternative medications, occasionally at the expense of best clinical practices. This creates a conflict wherein both physicians and patients may find brand-name medications clinically superior but nevertheless choose generic ones. The issue of generic versus brand medications is a key component of the discussion of health payers, physicians and their patients. This review evaluates some of the important medications in the armamentarium of pain physicians that are frequently used in the management of chronic pain, and that are currently at the forefront of this issue, including Opana (oxymorphone; Endo Pharmaceuticals, Inc., Malvern, PA), Gralise (gabapentin; Depomed, Newark, CA), and Horizant (gabapentin enacarbil; XenoPort, Santa Clara, CA) that are each available in generic forms as well. We also discuss the use of Lyrica (pregabalin; Pfizer, New York, NY), which is currently unavailable as generic medication, and Cymbalta (duloxetine; Eli Lilly, Indianapolis, IN), which has been recently FDA approved to be available in a generic form. It is clear that the use of generic medications results in large financial savings for the cost of prescriptions on a national scale. However, cost-analysis is only part of the equation when treating chronic pain patients and undervalues the relationships of enhanced compliance due to single-daily dosing and stable and reliable pharmacokinetics associated with extended-duration preparations using either retentive technologies or delayed absorption strategies. Medications given to chronic pain patients should be individualized to best serve analgesic needs and assure patient safety primarily, based on high levels of scientific and economic evidence. Decisions regarding utilization should not be made based solely on limited or faulty assessments of cost–benefit analyses.