This report is a review of some of the results obtained over the course of 20 years spent investigating hemoglobin phenotypes and the related functional effects on hematological patterns in ruminant breeds. Tests included qualitative and quantitative analyses of hemoglobins and qualitative and quantitative analyses of α and β globins, as well as hemochromocytometric analysis. Understanding the adaptive significance of the hemoglobin variants was the goal of most of these investigations. The advances presented in this review and the previously unpublished findings included here provide evidence that Mediterranean breeds exhibit a fair number of positively charged variants, whose possible adaptive significance is discussed.