End-stage heart failure is a chronic illness with a high death rate, few medical treatment options, and limited resources. For decades, long term use of inotropes have been essential in the treatment of acute cardiogenic shock. While inotropes increase cardiac output, they are associated with an increased risk of death due to tachycardia and increased oxygen consumption. Inotropes are currently used to improve cardiac activity by amplifying normal calcium entry pathways into cells, however, this requires a lot of energy, which has negative effects. If this energy was somehow to be conserved, then it could be used to regenerate cells and promote mitochondrial health and reduce oxidative stress. It is hoped that the next generation of inotropic agents would improve myocardial performance without shortening velocity or facilitating unnecessary calcium modulation at the SR or L-type calcium channel level. The arrival of new agents is on the horizon. The procedures used to investigate their protection and effectiveness, on the other hand, may be difficult. On top of that, end stage heart failure patients are inherently complex, posing a slew of additional obstacles. Clinical studies of this patient population are expected to remain costly, complex, and unclear in terms of proper end points. However, despite the many challenges and disappointments, the search for these safer positive inotropic medications has persisted and seems to be succeeding.