The research on noncoding RNAs has come a long way since the realization that these RNA molecules hold a lot of promise, particularly in terms of diagnosis, prognosis, and perhaps treatment of several human diseases. A number of noncoding RNAs, ranging from linear microRNAs and long-noncoding RNAs to circular RNAs, and several others are now under investigation. A logical way forward is the testing of these noncoding RNAs to bring them from bench to diagnostic laboratories, clinics, and bedside. However, the transition has not been very smooth, and even challenging at times, because of the unique nature of these biological molecules and the expertise and fine technologies needed to evaluate them, along with the refinement of methodologies to deliver them as therapeutics. This chapter specifically focuses on the associated challenges, such as expression/detection, target validation, immunogenicity, and delivery, that are hampering the utilization of noncoding RNAs in clinics.