Cystic fibrosis (CF) is characterised by a build-up of thick, intransient mucus linings of the digestive and respiratory mucosa, which disrupts digestive system functioning and microbiota composition. In view of the potential for probiotics to enhance microbiota composition in other contexts, this study investigated the current evidence for probiotics as an adjunct to usual therapy for CF. Electronic clinical databases were interrogated for human randomised, controlled, intervention trials (1985–2015) testing the effects of probiotics on clinical endpoints in CF were reviewed. From 191 articles identified in initial searches, six studies met the critical inclusion criteria, and were reviewed in detail. These studies varied in size (n = 22 to 61) but were generally small and showed substantial diversity in protocol, specific probiotic species used and range of clinical outcomes measured. Probiotic administration showed beneficial effects on fecal calprotectin levels, pulmonary exacerbation risk, and quality of life indicators. In one study, such changes were associated with variations in gut microbiota composition. Despite encouraging preliminary results, the limited number of small and highly varied studies to date do not justify the addition of probiotics as an adjunct to current CF treatment protocols. Importantly, very minimal adverse effects of probiotics have been reported.