Investigations to explore human handedness have been conducted for ages. It is still uncertain what causes people to use the left or the right hand. Clues supporting the genetic origin of handedness have been accumulating and provide the best evidence. Nevertheless, in some populations there are added proportions of left-handedness that do not seem to be explained solely by genes. The term pathological left-handedness has emerged around 30 years ago, referring to some right-handers who became left-handed due to an early life brain insult. In this thesis an attempt is made to revisit pathological left-handedness, exploring some of its origins and possible later life health outcomes. Studies on origins of left-handedness were conducted in populations which are at higher risks of having early life brain damage, such as prematurely born children and survivors of childhood meningitis. Studies on possible outcomes associated with left-handedness were done in healthy populations of adults at risk for specific health consequences. Indicators of early life brain damage seemed to be related to a higher risk of becoming left-handed. Furthermore, being left-handed seemed to increase the risk of getting premenopausal breast cancer, psychological and physical distress, and mortality, especially due to cancer and cerebrovascular diseases. Studying handedness, which is only one aspect of overall laterality, is a complex process. The results of the studies in this thesis should be an inspiration for further research into the concept of pathological left-handedness.