The ongoing evolution of genomics and bioinformatics has an overwhelming impact on medical and clinical research, albeit this development is often marked by genuine controversies as well as lack of scientific clarities and acumen. The search for disease genes and the gene–environment interaction has drawn considerable interdisciplinary scientific attention: environmental health, clinical and medical sciences, biological as well as computational and statistical sciences are most noteworthy. Statistical reasoning (quantitative modeling and analysis perspectives) has a focal stand in this respect while data mining resolutions are far from being statistically fully understood or interpretable. The use of human subjects, though unavoidable, under various extraneous restraints, medical ethics perspectives, and human rights undercurrents, has raised concern all over the world, especially in the developing countries. In the genomics context, clinical trials may be designed on chips and yet there are greater challenges due to the curse of dimensionality perspectives. Some of these challenging statistical issues in medical and clinical research (with emphasis on clinical trials) are appraised in the light of existing statistical tools, which are available for less complex clinical research problems.