In Falling Skies, human civilization at a global scale collapsed following the Espheni invasion. An Espheni EMP (Electro Magnetic Pulse) knocked out many electrical devices which the humans relied greatly on, crippling their ability to fight. Without their computers, advanced communications systems, and powerful weapons, humans were easy targets for the Espheni; the children were taken and harnessed for use as soldiers and slave laborers, and the adults were massacred. The survivors formed into local resistances, working to fight off the occupation.
Its revealed that 1,500 years before the current Invasion of Earth, the Espheni tried to invade. That time, the Espheni underestimated humanity and the Espheni forces' leader, the Espheni Queen's own daughter, was killed. The Espheni Queen vowed to return a thousand times stronger and wipe out humanity, the true reason for the Espheni attack on Earth. (Reborn)
Despite being severely outmatched, many resistances have held out against the Espheni. The humans spirit, history, strength, and good leadership has given them the power to keep moving forward and keep surviving and fighting. The Skitter Rebellion and the arrival of the Volm marked turning points in the Human/Espheni war. The aid these groups both have given--despite having few soldiers working with the humans--has helped the Charleston group to make decisive blows against the Espheni on the Eastern Sea Board. Following the destruction of the Espheni Power Station, the Espheni's mechanical servants and technology is deactivated, resulting in them relying on organic servants, including clones of key people. Resistance leader Tom Mason takes advantage of this weakness to rally humanity into a Global Resistance and leads all of the United States militias in an assault on Washington, D.C. where the Espheni Queen is located. They are aided in their efforts by a surviving member of the Espheni's ancient enemy the Dornia who supplies the humans with a bioweapon that will wipe out the Espheni when used on their queen. In a final confrontation in the ruins of the Lincoln Memorial, Tom Mason infects the Espheni Queen and thus the entire Espheni race with the Dornia bioweapon. The bioweapon kills the Espheni and frees Earth from their control. With the Espheni now dead, the human race unites and gathers months later at the rebuilt Lincoln Memorial to elect a new leader for the united species.
In Season 4, over 2 years into the war the Espheni began experimenting on "skitterizing" humans. The process is still incomplete as a few humans, like Jeanne Weaver still retain some free will and memory. In Season 5, sometime later they are still perfecting the process. Caitlin informs the 2nd Mass that while he may lash out at her, her skitterized brother Brian shows remorse towards his actions.(Hunger Pains) Human Skitterization has been apparently discontinued in both forms (children and adults) since the destruction of the Espheni Power Core which rendered harnesses and Espheni mutation devices useless. During the Assault on Washington, D.C., it was discovered that Skitterized-humans had been used to build a powerful defensive wall around the city, but they aren't actually seen themselves. The Skitterized humans are killed along with all the other Espheni by the Dornia bioweapon. (Reborn)