This review article was written for people like Paul McGhee when he was 20 years old: curious and interested in the neurology and psychiatry of humor, smiling and laughter but neither physicians nor experts in cognitive science. It begins with necessary reflections on what it even means to consider humor, smiling and laughter from within these disciplines. These frames of reference, useful as they are, are far from neutral. The reader is encouraged to be sensitive to some logical and linguistic pitfalls that can fatally endanger meaningful discussions of these subjects. The results of empirical studies of humor, smiling and laughter which have employed the tools of neurology and psychiatry are then reviewed, roughly in the order in which the techniques have emerged historically, beginning with clinical studies (Part I) and continuing with current studies employing functional imaging methods in Part II. Therapeutic approaches using humor, smiling and laughter, particularly with respect to neurological and psychiatric diseases – but also including other diseases – are discussed. Finally a short synopsis of what is known about the neurology and psychiatry of humor, smiling and laughter is presented.