A properly validated biological marker (biomarker) would offer undeniable value as a prognostic or diagnostic indicator of a disorder and/or its response to a therapeutic intervention. However, upon their discovery, a biomarker candidate must traverse a rigorous and exhaustive testing protocol aimed to challenge the validity of its proposed application. This validation trajectory establishes both the quality of a biomarkers analytical testing protocol and the efficacy of its clinical utilization. The successful completion of such testing is a requisite for the acceptance of a biomarkers intended surrogacy. Such testing also prevents the premature translation of invalid putative markers into an environment in which they may inflict unintended harm to a patient or public health more generally. To aid in their potential clinical translation, numerous publications have described detailed evaluation and validation protocols for putative biomarkers. These also serve as an aid to prevent promising putative indicators from being lost in the often complex bench-to-bedside translation and/or drug development process. However, convergent and divergent views do remain among stakeholders in terms of the evidentiary framework(s) that should be applied on the biomarker innovation trajectory. Such guidelines, policy statements and recommendations detail and shape the relevant tenets for biomarker assessment and validation. An overview of these analytical and clinical schemas and their experimental principles are provided in this paper. Such protocols represent examples of both the fundamental research required for evaluating newly discovered putative biomarkers and the scientific communitys attempts to bridge the current translation chasm facing biomarker research on the critical path to personalized medicine. Further, these concepts are directly applicable to parallel personalized medicine and biomarker research being undertaken in developing countries and resource limited settings.