Many environmental and lifestyle related factors may influence the physiology of the brain and body by acting on fundamental molecular pathways, such as the hypothalamus-pituitary-adrenal axis (HPA) and the immune system. For example, stressful conditions created by adverse early-life events, unhealthy habits and low socio-economic status may favor the onset of diseases linked to neuroendocrine dysregulation, inflammation and neuroinflammation. Beside pharmacological treatments used in clinical settings, much attention has been given to complementary treatments such as mind-body techniques involving meditation that rely on the activation of inner resources to regain health. At the molecular level, the effects of both stress and meditation are elicited epigenetically through a set of mechanisms that regulate gene expression as well as the circulating neuroendocrine and immune effectors. Epigenetic mechanisms constantly reshape genome activities in response to external stimuli, representing a molecular interface between organism and environment. In the present work, we aimed to review the current knowledge on the correlation between epigenetics, gene expression, stress and its possible antidote, meditation. After introducing the relationship between brain, physiology, and epigenetics, we will proceed to describe three basic epigenetic mechanisms: chromatin covalent modifications, DNA methylation and non-coding RNAs. Subsequently, we will give an overview of the physiological and molecular aspects related to stress. Finally, we will address the epigenetic effects of meditation on gene expression. The results of the studies reported in this review demonstrate that mindful practices modulate the epigenetic landscape, leading to increased resilience. Therefore, these practices can be considered valuable tools that complement pharmacological treatments when coping with pathologies related to stress.