Reading music and playing a musical instrument is a complex activity that comprises motor and multisensory (auditory, visual, and somatosensory) integration in a unique way. Music has also a well-known impact on the emotional state, while it can be a motivating activity. For those reasons, musical training has become a useful framework to study brain plasticity. Our aim was to study the specific effects of musical training vs. the effects of other leisure activities in elderly people. With that purpose we evaluated the impact of piano training on cognitive function, mood and quality of life (QOL) in older adults. A group of participants that received piano lessons and did daily training for 4-month (n = 13) was compared to an age-matched control group (n = 16) that participated in other types of leisure activities (physical exercise, computer lessons, painting lessons, among other). An exhaustive assessment that included neuropsychological tests as well as mood and QOL questionnaires was carried out before starting the piano program and immediately after finishing (4 months later) in the two groups. We found a significant improvement on the piano training group on the Stroop test that measures executive function, inhibitory control and divided attention. Furthermore, a trend indicating an enhancement of visual scanning and motor ability was also found (Trial Making Test part A). Finally, in our study piano lessons decreased depression, induced positive mood states, and improved the psychological and physical QOL of the elderly. Our results suggest that playing piano and learning to read music can be a useful intervention in older adults to promote cognitive reserve (CR) and improve subjective well-being.