Over the past two decades, high-throughput (HTP) technologies such as microarrays and mass spectrometry have fundamentally changed clinical cancer research. They have revealed novel molecular markers of cancer subtypes, metastasis, and drug sensitivity and resistance. Some have been translated into the clinic as tools for early disease diagnosis, prognosis, and individualized treatment and response monitoring. Despite these successes, many challenges remain HTP platforms are often noisy and suffer from false positives and false negatives; optimal analysis and successful validation require complex workflows; and great volumes of data are accumulating at a rapid pace. Here we discuss these challenges, and show how integrative computational biology can help diminish them by creating new software tools, analytical methods, and data standards.