Neurologic Differential Diagnosis: A Case-Based Approach (A. B. Ettinger and D. Weisbrot, eds., Cambridge University Press), published in 2014, emphasizes a pragmatic and quick-reference approach to achieving a comprehensive differential diagnosis. Using this text, the clinician can efficiently look up specific symptoms and signs such as “dizziness,” “mental status change,” “diplopia,” “foot drop,” or “psychosis” to immediately generate diagnostic possibilities. Each chapter outlines key features of clinical presentations and quickly reminds the clinician what diagnoses to consider. While our prior textbook helps the clinician to rapidly generate a differential diagnosis, an additional approach would also be invaluable. Symptoms and signs in neurology and psychiatry do not typically occur in isolation; rather, they present in the clinical context of other underlying conditions. For example, a physician evaluating a 40-year-old male with change in mental status could utilize Neurologic Differential Diagnosis: A Case-Based Approach to review a diverse list of potential underlying diagnoses. However, if it is known, for example, that this patient carries a diagnosis of HIV, the clinician would also consider what complications of HIV are associated with mental status changes. These include AIDS dementia complex, central nervous system (CNS) lymphomas, cryptococcal meningitis, CMV superinfections, neurosyphilis, toxoplasmosis, and other conditions that occur in immunocompromised states. Having a checklist of these conditions enables the clinician to quickly access information on the neurologic and psychiatric complications of co-existing conditions such as HIV, and this further enhances the busy clinician’s attempt to provide a comprehensive evaluation. What about a 30-year-old woman with epilepsy who now complains of headaches? While the broad differential diagnosis as described in our earlier textbook includes seizures and postictal states or nonepileptic conditions such as migraine or subarachnoid hemorrhage, this patient happens to have been recently started on lamotrigine to treat seizures. Could lamotrigine be responsible for the headaches? A review of a succinct summary of lamotrigine’s neurologic or psychiatric adverse effects would describe headaches, including uncommonly encountered aseptic meningitis. This in turn would lead the clinician to perform additional investigations.