Although pain is a common fear to most, our overall ability to recognize pain, and assess and intervene with appropriate therapies is mediocre at best. However, if made a priority, substantial gains can be made in improving patient satisfaction with pain control and in rectifying deficits in the knowledge of health-care professionals. This goal is not easily obtained and generally requires time, patience, and a multidisciplinary team approach. Pain can induce numerous metabolic and neuroendocrine responses. While seemingly homeostatic, these changes can have significant physiologic and sometimes adverse consequences. Anesthesia and analgesia, especially by way of neural blockade, can alleviate some of the changes and sometimes improve unwanted consequences. While at times these techniques have not significantly altered outcome, at other times significant benefits have been observed. More sophisticated techniques and pharmacotherapies are being developed and introduced with increased frequency, but alone they will probably have only minimal impact on overall morbidity and mortality. The integration of a multimodal approach seems logical in the critical care setting, with analgesia as the cornerstone.