Over the past 70 years, the incidence of syphilis has dramatically decreased and consequently the neurosyphilis one. Therefore, when a patient is presented with neuropsychiatric symptoms such as psychosis, mania, memory loss, neurocognitive troubles, attention deficits, behavioral changes, or depression, a neurosyphilis diagnosis is not the first that comes to a clinician’s mind. In fact, many times, patients are first treated with psychiatric medication when penicillin would be the appropriate line of treatment. In this article, after we review neurosyphilis, we report 11 clinical cases with neuropsychiatric manifestations of syphilis and make the case for careful syphilis screening in patients presenting with psychiatric and neurological symptoms.