Numerous pharmaceuticals, materials, and fine chemicals are synthesized by homogenous transition metal catalysis. The power of homogenous catalysis stem from the fact that both the reactivity and selectivity of a given catalyst can be tuned by modifying the structure of the catalyst's ancillary ligands. In this seminar, our recent research efforts to address two unsolved challenges in ligand design are discussed. The first part will focus on the discovery of mono-N-protected amino acid (MPAAs) as ligands to promote C-H activation at palladium(II) centers. The second part will describe a model to explain and predict initiation rates in ruthenium-based olefin metathesis catalysts containing chelating ortho-alkoxybenzylidene ligands. Key underlying principles from these investigations will be highlighted to guide future iterations of catalyst development