Venous congestion and endothelial and neurohormonal activation are known to occur in acute decompensated heart failure (ADHF), yet the temporal role of these processes in the pathophysiology of decompensation is not fully understood. Conventional wisdom presumes congestion to be a consequence of worsening cardiovascular function; however, the biomechanically driven effects of venous congestion are biologically plausible contributors to ADHF that remain largely unexplored in vivo. Recent experimental evidence from human models suggests that fluid accumulation and venous congestion are not simply consequences of poor cardiovascular function, but rather are fundamental pro-oxidant, pro-inflammatory, and hemodynamic stimuli that contribute to acute decompensation. The latest advances in the monitoring of volume status using implantable devices allow for the detection of venous congestion before symptoms arise. This may ultimately lead to improved treatment strategies including not only diuretics, but also specific, adjuvant interventions to counteract endothelial and neurohormonal activation during early preclinical decompensation.