Sickle Cell Acute Chest Syndrome remains the leading cause of death in patients suffering from Sickle Cell Disease. In his Best Case Ever, Dr. Richard Ward, a hematologist with a special interest in Sickle Cell Disease, describes a case of a Sickle Cell Disease patient who presents with what appears to be a simple pain crisis, but turns out to be a devastating Acute Chest Syndrome. He gives us the key clinical pearls and pitfalls to make this often elusive diagnosis early so that life-saving treatment can be initiated in a timely manner. This is in anticipation of the upcoming episode on The Emergency Management of Sickle Cell Pain Crisis with Dr. Ward and Dr. John Foote.