Research in the past decade has shown that variations in the gut microbiome may influence behavior, and vice versa. As such, interest in the role of the gut microbiome in psychiatric conditions has drawn immense interest. This is evidenced by the recent surge in published studies examining microbial dysbiosis in clinical psychiatric populations, particularly autism spectrum disorder and depression. However, critical examination of these studies reveals methodological flaws in design and execution, suggesting that they may not be held to the same standards as other bodies of clinical research. Given the complex nature of the gut microbiome, this narrative review attempts to clarify concepts critical to effectively examine its potential role in psychopathology to appropriately inform mental health researchers. More specifically, the numerous variables known to affect the gut microbiome are discussed, including inflammation, diet, weight, and medications. A comprehensive review of the extant microbiome literature in clinical psychiatric populations is also provided, in addition to clinical implications and suggestions for future directions of research. Although there is a clear need for additional studies to elucidate the gut microbiome's role in psychiatric disorders, there is an even greater need for well-designed, appropriately controlled studies to truly impact the field.