Lifeform extinctions have been common throughout Earth's history. It is estimated that more than 99.9% of all species have now become extinct.
There have been many extinction events, both great and small, but the most profound of these would be the Great Permian Extinction that ended the Palaeozoic era (252 Ma). Also known as the Great Dying, it is thought that over 90% of all marine species and 70% of all terrestrial species became extinct during this period. It is still unclear what caused this major extinction event - hypotheses include multiple meteor impacts and proximity to a local supernova - but the prevailing hypothesis is that it was caused by a flood of lava across the surface of the Earth. Situated in Northern Russia and known as the Siberian Traps these lava fields covered an area of seven million square kilometres, releasing huge amounts of carbon dioxide into the atmosphere. This destructive environmental shift may have been further exacerbated by the rapid bloom of methane producing Archaean organisms (Methanosarcina) - feeding on minerals within the lava fields - deepening the global catastrophe. The rapid increase in surface temperatures brought about a collapse in the carbon cycle - starving life on land and subsequently suffocating life in the seas. No environmental niche was left unchanged by the Permian Extinction. However it would be incorrect to think that all life was nearly wiped from the planet by this event at the end of the Palaeozoic era.
Life on Earth has never been tentative - aside from possibly the first few moments of its arrival. From the earliest ages of the planet, when microbial blooms spread around the globe, up to the radiation of Homo sapiens, life has repeatedly colonised every viable location on the planet. Life is nothing if not resilient and great extinctions serve to highlight this. Even if only a few isolated pockets of single-celled organisms survived a global extinction event - an event even more destructive than the Great Permian Extinction - life would continue on, evolving, adapting and radiating back across the world as soon as conditions allow.
Until the dying Sun consumes the Earth there will be no end to life on the planet.