Maintaining a healthy brain is a critical factor for the quality of life of elderly individuals and the preservation of their independence. Challenging aging brains through cognitive training and physical exercises has shown to be effective against age-related cognitive decline and disease. But how effective are such training interventions? What is the optimal combination/strategy? Is there enough evidence from neuropsychological observations, animal studies, as well as, structural and functional neuroimaging investigations to interpret the underlying neurobiological mechanisms responsible for the observed neuroplasticity of the aging brain? This piece of work summarizes recent findings toward these questions, but also highlights the role of functional brain connectivity work, an emerging discipline for future research in healthy aging and the study of the underlying mechanisms across the life span. The ultimate aim is to conclude on recommended multimodal training, in light of contemporary trends in the design of exergaming interventions. The latter issue is discussed in conjunction with building up neuroscientific knowledge and envisaged future research challenges in mapping, understanding and training the aging brain.