Tracing the reaction pathways of complex organometallic and bio-inorganic systems is a challenging field in theoretical and computational chemistry; indeed, the variety of metal-substrate interactions coupled to the large dimensions of the investigated systems often result in extremely complex potential energy surfaces, characterized by a large number of local minima and transition states connecting the reagents and products basins. The power of Density Functional Theory (DFT) calculations combined to DFT-based molecular dynamics simulations, by means of the Car-Parrinello method [1], is illustrated considering examples of applications in the field of bio-inorganic catalysis ranging from the electronic structure and reactivity of bio-mimicking oxidants to models of the photosynthetic system II. Also, the role of protein environment on CO-O2 selectivity [2] in myoglobin and its implications in CO/O2 myoglobin photochemistry [3] are analysed considering TD-DFT excited states calculations and simulations including extended portions of the protein pocket at a full quantum-chemical level.[4] References: [1] Car, R.; Parrinello, M. Phys. Rev. Lett., 1985, 55, 2471. [2] De Angelis, F.; Jarzecki, A.J.; Car, R.; Spiro, T.G., J. Phys. Chem. B, 2005, in press. [3] De Angelis, F.; Car, R.; Spiro, T.G., J. Am. Chem. Soc., 2003, 125, 15710. [4] Giannozzi, P.; De Angelis, F.; Car, R. J. Phys. Chem., 2004, 339, 204.