The majority of articles selected for this chapter refer to novel pathophysiological mechanisms that have recently been elucidated. Levels of expression and methylation as well as specific polymorphisms in the IGF2 gene were shown to play a key role not only in fetal growth but also in early postnatal weight gain. IGFBP-4 was reported to be a key mediator between nutrition and adipose tissue expansion. FGF21 was shown to exert anti-inflammatory and antifibrotic actions in adipose tissue of db/db mice and to improve functional and morphological features of kidneys in diabetic nephropathy. IGF-I was revealed to stabilize the atherosclerotic plaque by enhancing the synthesis of collagen type 1. GH, through the activation of EGF receptor, was described to restore the liver regeneration capacity impaired by steatosis. Interplay between SIRT1 and the GH/IGF-I axis was reported to represent a crucial adaptive response to fasting in the liver. GH was even demonstrated to block the progression to type 1 diabetes in NOD mice by favorably modulating the immune response. Finally, the mechanism of the year is undoubtedly the elucidation of JAK2 activation by the GH receptor, which represents a molecular model common to all class I cytokine receptors. All of these novel mechanisms and actions were identified in animal and/or cellular models, thus making their translation into human physiology as well as clinical utility a working hypothesis to be tested in the near future. Nevertheless, this body of experimental knowledge about mechanisms directly or indirectly involved in many human pathologies may be considered a significant leap forward for the development of new therapeutic strategies based on the modulation of growth factors.