In this chapter we explore mindfulness theory and practice, and what we have learnt from behavioural science and neuroscience about its effects and its mechanisms of action. While there has been a great deal of hype about mindfulness, and there are many poorly conceived or inadequately evaluated programs, the growing body of evidence is unequivocal about its direct and indirect benefits for improving mental health and promoting well-being, along with increases in compassionate care for oneself and others. We describe the application of mindfulness meditation training in a healthcare setting to enhance the well-being of nurses and their ability to provide compassionate care. Both individual and organisational level factors are examined in relation to the successful implementation of the mindfulness training program to nurses and senior staff in the Sydney Local Health District (SLHD). What we have learned, and share with readers is that the key to the success of a large-scale mindfulness program in an organisation is the manner in which mindfulness training is integrated into the values and aims of the organisation and the way the program is promoted, designed and implemented.