Although known for millenia, it is only recently that mechanochemistry has caught serious attention by many chemists. Indeed, during the past 15 years an extraordinary number of reports concerning solid-state chemical transformations through grinding and milling techniques has been recorded. This short review discusses the circumstances that led to such renaissance, highlighting the present intense interest in so-called green chemistry, the enabling capacity of mechanochemistry to handle insoluble substrates, and the finding of the profound influence that additives can have on mechanochemically activated reactions. The core of this account focuses on salient developments in synthetic organic chemistry, especially in amino acid and peptide mechanosynthesis, the successful employment of mechanochemical activation in combination with asymmetric organocatalysis, the promising combination of mechanochemical activation with enzymatic and whole cell biocatalysis, and the remarkable achievement of multicomponent selective reactions via complex, multistep reaction pathways. The final section is dedicated to comment on some pending tasks in the area, such as scaling-up of milling processes to be of practical use in the chemical industry, the requirement of easier and more efficient control of reaction parameters and monitoring devices, and consequently the careful analysis of additional procedures for a proper understanding of mechanochemical phenomena.