Congestive heart failure is increasing in prevalence in the United States, and associated morbidity and mortality remain high. Aggressive treatment of decompensated heart failure is associated with improved outcomes; however, therapies must be tailored to the presenting characteristics of each patient and most carry a risk of adverse events stemming from the pharmaceutical itself. Nesiritide is approved for the treatment of acutely decompensated heart failure, but aggregate data analysis has suggested that it may be associated with a risk of excess mortality and worsening renal insufficiency. We review the recent evidence regarding the efficacy and safety profile of nesiritide, and discuss upcoming trials designed to address concerns regarding safety and the comparative efficacy of nesiritide.