Over recent years there have been major advances in our understanding of tumour biology which have led to improved diagnostic and prognostic techniques and the development of novel targeted therapies. However the reliability of such biomarkers is questionable and the efficacy of new treatments remains predominantly limited by a combination of drug resistance, toxicity and persisting insufficiencies in our comprehension of tumour-signalling pathways. Following their recent discovery, microRNAs (miRNAs) have been established as key regulators of gene-expression, and their putative roles as oncogenes and tumour suppressor genes has provided a potentially new dimension to our clinical approach to cancer diagnosis and treatment. Their role as biomarkers and therapeutic targets is appealing but several obstacles have as yet limited our ability to translate this potential into a clinical reality. This review focuses on currently accepted roles of miRNAs in cancer pathogenesis, and highlights the challenges and breakthroughs in this field to date with relevance to the cancer clinic.