We have seen it all in cancer treatment. We work with tree extracts, marine sponges, viruses, soil extracts, and many other things. Nature has giving us the tools to treat this threatening disease and will continue to do so if we have an open mind and are willing to learn; and we have gained extensive knowledge from the rapamycin story. It all started in a far-far away Island (Easter Island) with a soil bacteria and the identification of a microcyclic antibiotic with antifungal properties.

Twenty years later. We know (or we think we know) the target of rapamycin (TOR), the TOR complexes, the upstream and downstream effectors, the elements that activate or inhibit the pathway, and we start seeing the promising effects of targeting mammalian target of rapamycin (mTOR) not only in cancer but also other conditions such as inflammation and aging. We have the mother compound rapamycin approved for graft rejection, and we have rapamycin-coated arterial stents. We have three rapamycin analogs with improved pharmacological properties and we use them to treat various malignancies [1–4]. We all have seen patients benefiting from the treatment with rapalogs and doing remarkably well for prolonged time with almost no change in the quality of life. We are very familiar with the toxicity profile of rapalogs and we believe they are safe and compatible with prolonged use [5]. We are further fascinated about how the rapamycin story unfolds as we learn about rapalogs prolonging life-span in animals or reducing the inflammation [6, 7]. We also start to understand the mechanisms of resistance to mTOR inhib-