Abstract: This article provides a best evidence-informed review of the current scientific understanding of myofascial trigger points with regard to their etiology, pathophysiology, and clinical implications. Evidence-informed manual therapy integrates the best available scientific evidence with individual clinicians’ judgments, expertise, and clinical decision-making. After a brief historical review, the clinical aspects of myofascial trigger points, the interrater reliability for identifying myofascial trigger points, and several characteristic features are discussed, including the taut band, local twitch response, and referred pain patterns. The etiology of myofascial trigger points is discussed with a detailed and comprehensive review of the most common mechanisms, including low-level muscle contractions, uneven intramuscular pressure distribution, direct trauma, unaccustomed eccentric contractions, eccentric contractions in unconditioned muscle, and maximal or sub-maximal concentric contractions. Many current scientific studies are included and provide support for considering myofascial trigger points in the clinical decision-making process. The article concludes with a summary of frequently encountered precipitating and perpetuating mechanical, nutritional, metabolic, and psychological factors relevant for physical therapy practice. Current scientific evidence strongly supports that awareness and working knowledge of muscle dysfunction and in particular myofascial trigger points should be incorporated into manual physical therapy practice consistent with the guidelines for clinical practice developed by the International Federation of Orthopedic Manipulative Therapists. While there are still many unanswered questions in explaining the etiology of myofascial trigger points, this article provides manual therapists with an up-to-date evidence-informed review of the current scientific knowledge.