In 2005, surveillance systems first detected human cases infected with the swine-origin triple-reassorted influenza H1N1 virus. Four years later, this virus increased its transmissibility among human populations. In March of 2009, the further molecular changes of these triple-reassorted influenza H1N1 viruses were identified from the clustering patients with influenza-like illness in California, Texas, and Mexico. Within almost two and half months, this novel influenza H1N1 virus spread worldwide, attacked 112 countries and resulted in 59,814 cases and 263 deaths by June 26, 2009. The 2009 outbreak has given rise to potential public health threats caused by novel influenza viruses. In the upcoming autumn and winter seasons, we will definitely have to face greater challenges from transnational spreading, formulating public health policies to containing community outbreaks. All these need systematic thinking, inter-disciplinary research and international collaboration to reach the goal of global health.