Elevated NPs levels have shown predictive value in various diseases that have direct or indirect influences on the heart functions in many non-HF circumstances, even in the absence of depressed cardiac function. It should be noted that NPs should never be interpreted without thorough clinical messages. NPs are very sensitive for primary or secondary cardiac dysfunction, but the specificity is low. Potential clinical applications of NPs are expanded, accompanied by emerging reports regarding to screening for the presence of secondary cardiac dysfunction, monitoring the therapeutic responses, risk stratifications, or providing prognostic values in many settings. Clinical decision on timely and costly cardiac examinations or more risky and invasive procedures rather than deferred, conservative strategies might be facilitated by appropriate use and interpretation of NPs. However, clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, ruleout-diagnostic-tests (high NPV and low positive predictive values), monitoring of therapeutic responses, and prognosis of acute or decompensated CHF.