The search for basic concepts and underlying principles was at the core of the systems approach to science and technology. This approach was somehow abandoned in mainstream biology after its initial proposal, due to the rise and success of molecular biology. This situation has changed. The accumulated knowledge of decades of molecular studies in combination with new technological advances, while further highlighting the intricacies of natural systems, is also bringing back the quest-for-principles research program. Here, I present two lessons that I derived from my own quest: the importance of studying biological information processing to identify common principles in seemingly unrelated contexts and the adequacy of using known design principles at one level of biological organization as a valuable tool to help recognizing principles at an alternative one. These and additional lessons should contribute to the ultimate goal of establishing principles able to integrate the many scales of biological complexity.
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