The measurement of sweat chloride concentration (sweat test) remains the gold standard for the diagnosis of cystic fibrosis (CF). For infants with a positive newborn screening test for CF, the sweat test is the next step to confirm the diagnosis. However, there are several reports in the literature regarding conditions that are known to be associated with false positive or false negative sweat tests. This systematic review of the literature summarizes the evidence available regarding these conditions. Interpretation of sweat test results should be done in the context of patient's clinical presentation and associated comorbidities. Additional research is needed for conditions that may affect sweat chloride concentrations.