New epidemiological findings recast pain in sickle-cell disease (SCD) as being more often a chronic manifestation than was previously thought, although acute pain is still the hallmark of the disease. SCD pain intensity, the number of painful locations, and the frequency of hospitalizations due to SCD pain may worsen with age. In adults and even in children, the quantity and severity of SCD pain may be vastly underestimated, because most of the "iceberg" of SCD pain is "submerged" at home, and only the tip of the iceberg is seen by health care providers when acute SCD care is rendered in emergency rooms and hospitals. Implications of this "iceberg phenomenon" are significant for clinicians, researchers, employers, policy makers, and the public. Nevertheless, both emergency room and hospital utilization for SCD pain remain prevalent. Often, utilization recurs early, perhaps emblematic of poor acute pain management. New data show the protean impacts of SCD pain on health-related quality of life, sleep, and psychological and social health. The relationship of the severity of SCD pain to the severity of underlying sickle vasculopathy is unclear, but epidemiologic evidence and patient descriptors suggest a temporal evolution of pain mechanisms. At first, increasingly worse nociceptive pain from vaso-occlusion and local lesions may evolve over the first two decades of life. Then, in the third and following decades, central neuropathic pain may also evolve due to past and continuing nociceptive stimuli. New findings confirm environmental contributors to SCD pain, including seasonal (colder) temperatures, barometric pressure, and wind speed.