In Western societies the process of aging is closely related to the onset of chronic diseases, such as coronary artery disease, diabetic nephropathy or different types of malignancies. Novel biomarkers are urgently needed to assist in managing these diseases. Parallel to technical advancements possibilities for the analysis of the human proteome for biomarkers have recently made considerable progress. In a first part, this article attempts to describe the main proteomic platform technologies, their advantages and disadvantages and will critically review proteomic study design aspects necessary to obtain valuable data, such as choosing suitable clinical specimens, data processing and mining. Physiological age-related alterations in the human proteome have been described and were similar to indolent changes associated with chronic diseases, in particular of the kidneys. Therefore, in a second part this review will introduce several examples for the application of clinical proteomics to aging itself and age-related diseases. Several recent proteome studies with clinically sound designs are available. These performed careful validation in blinded cohorts. It is anticipated that a boost in disease-related proteomic data is expected in the very near future. However, lessons of the past teach the strict adherence to proper technological approaches, appropriate statistics, and large databases to fulfil these high expectations.