Despite the progress in pharmacotherapy, interventional cardiology (PPCI) and cardiac surgery of acute myocardial infarction (AMI), gradual post-AMI progression of myocardial dysfunction leads to heart failure (HF). Its increasing incidence represents a serious danger especially in the elder population challenged with further comorbidities, the prognosis being more unfavourable in females. Pathophysiological mechanisms of HF are complex and involving processes such as hemodynamic overload, ischemia, fibrosis, inflammation, ventricular remodelling, neurohumoral disbalanse, altered gene expression and Ca2+ cycling, oxidative stress, acceleration of apoptosis and mitochondrial dysfunction that subsequently leads to progressive decline of heart function and increased morbidity and mortality. Currently, neither effective prevention of AMI nor ultimate reduction of ischemia/ reperfusion (I/R) injury is available, therefore, there is an urgent need to search for alternative approaches based on the experimental findings. Ischemic preconditioning (PC) is a most robust form of innate cardioprotection based on the adaptation of the heart to I/R, which translation to clinical practice has been relatively successful albeit limited by technical requirements and short-term duration. Nevertheless, novel forms of adaptive interventions such as “remote“ PC (RPC) appear as promising beneficial approaches. Although molecular mechanisms of RPC are not yet completely elucidated, some forms of RPC, in particular its non-invasive modifications, have been already used in clinical conditions in patients with AMI, PPCI, congentital defects and bypass surgery, albeit with different effectiviness. We assume that in contrast to a traditional approach to pharmacological treatment of HF often focused on only one pathophysiological mechanism, a complex targeting of several pathophysiological mechanisms upon activation of intrinsic adaptive pathways represents a platform for the development of novel strategies to fight HF.