Disease dynamics are intimately connected to biological, environmental and social processes that take place at multiple scales and over various levels of social and biological organization. Further, in a highly interconnected world, epidemic outbreaks become instant potential health and/or economic global threats with increasing segments of the population playing active roles on the transmission patterns of infectious diseases like influenza. Individual and/or group actions and/or decisions and/or activities can enhance or reduce the effectiveness of intervention/control measures in the Information Era. Travel, social distancing, the availability of medical supplies (antiviral drugs and vaccine) and timely diagnostic tools, and the access to quality medical care are but some of the factors that have been identified as significant during this ongoing influenza pandemic. A fundamental challenge, then, is to find ways of integrating and grasping the processes and patterns that take place at key temporal scales and relevant levels of social and biological organization and use them to identify timely and effective intervention strategies. Despite the myriad of complexities associated with disease dynamics, macroscopic epidemic patterns emerge but finding effective ways of making use of this knowledge remain. How do we generate useful paradigms with the limitations inherent in reported epidemiological data or with the challenges posed by unreported disease data? Further, diseases experiencing rapid evolutionary changes, posing a tremendous threat to the viability of our limited drug supply. The evolution of resistance to antibiotics or antiviral drugs is one of the most important sustainability challenges that we face today, a challenge that must be central to the design and implementation of global public health policies. Will evolutionary changes at lower levels of organization, like cross-immunity, alter dramatically the epidemiological landscape at the population level? In this lecture I will address some of these challenges in a historical context starting with the work of physicians-theoreticians like Bernoulli, Ross, Kermack and McKendrick. The lecture will be tied in to the epidemiology of influenza with examples from the H1N1 ongoing pandemic.