Microalgae technology value is well known. Many achievements of the researchers highlight their potential to be used as a renewable energy source. Hence, focus will be given on microalgae as challenging competitive sources of biofuels. Development of cost-effective microalgae technology for biofuels requires the understanding and application of the biorefinery concept by the utilization of every component of biomass, recycling harvested water and using wastewaters as a source of nutrients for the growth of microalgae. The complexity of the whole productive chain where lipids are used for biodiesel requires the application of innovative decisions and mathematical methods for process development and photobioreactor (PBR) design and scale-up. This chapter analyzes the kinetics of the transesterification process of lipids to biodiesel as well as the mathematical approach as a powerful tool for the analysis and development of any unit operation, and influence of state parameters on microalgal growth. Special attention is given to microalgal strain selection, complex mathematical analysis of closed column PBR design whose effectiveness determines the success of overall technological scheme of biomass production, lipids, and other target metabolites.