Henry Rosenberg, MD† In one form or another, the following scenario is occurring daily in hospitals throughout the world: a 10-mo-old infant with progressive hypotonia and failure to thrive is scheduled for a surgical muscle biopsy and gastrostomy with general anesthesia. The neurological evaluation reveals a differential diagnosis that may include central white matter disease, metabolic encephalopathy, mitochondrial myopathy, or others. The neurologist recommends a nontriggering general anesthetic in the event that the infant is susceptible to malignant hyperthermia (MH). The anesthesiologist performs an uneventful general anesthetic with total IV anesthesia. Regardless of the results of the muscle biopsy, for each subsequent required anesthetic, a nontriggering technique is performed. What is the likelihood that any of these infants is truly MH-susceptible? This month’s issue of Anesthesia & Analgesia presents a series of articles that helps us answer this question more definitively, though inconclusively, than ever before. As hotline consultants for the Malignant Hyperthermia Association of the United States (MHAUS),* we commonly receive requests to help clinicians by defining the specific disease entities that predispose to MH susceptibility. With the exception of a small number of inherited conditions, the answer is elusive. With all of our knowledge to date on MH, why is this so? Because in clinical medicine, it is extremely difficult to establish definitive causal relationships without prospective randomized controlled trials, and cohort studies are impossible to perform for rare events. Therefore, we are left with a broad generalization derived from case control studies and case reports and series. To complicate matters, these historical reports did not have the benefit of genetic linkage and pedigree analysis which have, in the current era, furthered the definitive diagnosis of various syndromes and their link to MH. The path to this specialized issue on MH-associated diseases began several years ago when we and several other MHAUS hotline consultants hosted a series of panel discussions on MH at the annual meetings of the American Society of Anesthesiologists and the Society for Ambulatory Anesthesia. At the 2006 winter meeting of the Society for Pediatric Anesthesia (SPA), Barbara Brandom, Richard Kaplan, and Ron Litman participated on a panel of challenging pediatric MH cases. The response from the audience was overwhelming and clear: “Tell us who should and who shouldn’t receive a nontriggering technique.” Thus began a 3-yr process that now culminates with the articles presented herein. First, we identified international authoritative experts on each of the broad categories of diseases that have purportedly been linked to MH. Next, we created a partnership between SPA and MHAUS with the purpose of presenting a one-day symposium on MH-related diseases at the 2008 SPA winter meeting.† The organization and implementation of this symposium would not have been possible without the philosophical and financial support of SPA and MHAUS. By all accounts, the symposium was a resounding success. Each of our authorities presented a lecture on a specific category of disease and the From the *Department of Anesthesiology and Critical Care, The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; and †Saint Barnabas Medical Center, Livingston, New Jersey. Accepted for publication May 7, 2009. Address correspondence and reprint requests to Ronald S. Litman, DO, Department of Anesthesiology and Critical Care, The Children’s Hospital of Philadelphia, 34th St. & Civic Center Blvd., Philadelphia, PA 19104. Address e-mail to litmanr@email. chop.edu. Copyright © 2009 International Anesthesia Research Society DOI: 10.1213/ane.0b013e3181ae6b96 *Available at: http://www.mhaus.org. †Available at: http://www.pedsanesthesia.org/meetings/2008winter/spa08_program.pdf.