In clinical practice, serum level monitoring of anticonvulsant drugs is usually adequate. When there is an alteration in the binding of the anticonvulsant drug to the plasma proteins, however, the relationship between the serum concentration and therapeutic efficacy or toxicity becomes difficult to interpret. This can occur with combinations such as non-steroidal anti-inflammatory drugs (NSAIDs), phenytoin (Dilantin), carbamazepine (Tegretol), and valproic acid (Depakene) or when the albumin level is low. A failure to rely on serum free levels of the anti-convulsant under these circumstances can easily result in poor clinical decisions. The technique of serum free level measurement and illustrative examples of specific cases are provided to document the usefulness of this invaluable laboratory test.