Two of the major risks from an oil spill incident at sea are associated with the maritime transport and the coastal/offshore installations related to the oil and gas industry exploration and exploitation. Such risks call for preparations of the operational response to oil spill incidents, based on the lessons learned from the sinking of Exxon Valdez in 1989, Haven in 1991, Prestige in 2002, the Lebanon oil pollution crisis in 2006 and BP’s Deepwater Horizon offshore drilling platform catastrophe in 2010. There are several international and regional policies, which have been implemented for oil spill response, such as the MARPOL, Barcelona, and Black Sea Commission conventions. The conventions recognize pollution from oil spills as one of the major threats to the marine environment in regional seas, such as the Mediterranean Sea and the Black Sea. At the European Union (EU) level, the Member States were requested to implement various EU Directive concerning the response measurements for oil spill incidents, such as for example the EU 2005/35 aimed at identifying marine pollutes. The response to an oil spill incident requires various measures and engagement of various types of equipment and the success of the response as a whole depends greatly on the prediction of the movement and weathering of the oil spill. Such predictions can be obtained via an operational implementation of well-established numerical oil spill models, integrated with high resolution data, which may be downscaled from global and/or regional metocean forecasts. Numerous oil spill predictions systems were developed to predict the transport, diffusion, and the weathering processes of evaporation, emulsification, viscosity changes, dispersion and coastal impacts and adhesion of oil; only few of them provide predictions/parameterizations of oil plumes released from any given water depth, of biodegradation and the effects of ice. To this end, an overview of the transport and weathering processes incorporated in operational oil spill models is provided in this chapter, together with oil plumes biodegradation, and oil in ice parameterizations. Moreover, examples of best practices to assist the response agencies at regional and local levels in case of oil spillages are provided: the integration of routine satellite monitoring of oil slicks from SAR data with the oil spill models for short operational forward and backward trajectories predictions and harmonized multimodel approach for oil spill predictions, demonstrating the increase of confidence in oil spill modeling prediction, especially during long-term oil spill simulations using hind-cast metocean data to evaluate and assess the impact from potential and/or existing oil pollution sources at monthly, seasonal and interannual scales, to sensitive coastal and offshore infrastructures.