Abstract Hospitalizations for heart failure (HF) have become a global problem worldwide. Each episode of HF decompensation may lead to deleterious short- and long- term consequences, but on the other hand is an unique opportunity to adjust the heart failure pharmacotherapy. Thus, in-hospital and an early post-discharge period comprise an optimal timing for initiation and optimization of the comprehensive management of HF. This timeframe affords clinicians an opportunity to up titrate and adjust guideline-directed medical therapies (GDMT) to potentially mitigate poor outcomes associated post-discharge and longer-term. This review will cover this timely concept, present the data of utilization of GDMT in HF populations, discuss recent evidence for in-hospital initiation and up-titration of GDMT with a need for post-discharge follow-up and implementation this into clinical practice in patients with heart failure and reduced ejection fraction.