So it seems that, given the updates to health penalties, that the optimal strategy early on in the game is to continue to spam cities so long as one's health remains above -20 (-15 once Computing is discovered and espionage becomes a threat). Basically, send out as many settlers as you can without going below -20 . In each of the newly settled cities, build clinics, cytonurseries, and pharmalabs to offset the health penalties from cities (each city has a -4 before population is added), and then start another round of settling & conquering. Once you've progressed enough along technology wise and picked up several virtues, concentrate on restoring your empire's health and building up. Along the way one should also setup trade routes to bolster one's economy. I'm hard pressed to see why this strategy would fail to be near optimal (although, I confess I haven't fully tested it yet). Health penalties at various levels of health are: - 5 one suffers a penalty of -10% to growth -10 one suffers a penalty of -20% to growth -15 one suffers a penalty of -30% to growth and -5% to science -20 one suffers a penalty of -40% to growth and -10% to science There's a penalty to culture as well but that seems less important early on and easily recoverable later in the game. The penalty to science will never outstrip the marginal utility to building a new city. If you have N cities, that N + 1 city will add -9% (-5% per city + -4% for health penalty) penalty to science not including the population the city will add to your empire. Assuming that new city is comparable to the previous N cities in terms of its science potential, it's only a matter of time before that new city is generating more far science than that -9% penalty. The growth penalty is a bit more problematic but I still think the marginal utility of a new city outstrips the cost. Each new city dramatically increases your empire's growth potential, all else equal. The first city you build after your capital roughly doubles your growth potential, the second city increases it another third, and so on. Granted, your cities will be nothing more than large towns in the early game as you constantly build your empire out. However, any penalties your city generates sans population (-8% to growth due to the -4 penalty) will disappear once one builds a clinic, cytonursery, and pharmalab. The end result is, early in the game, the penalties an empire realizes due to health degradation per city will be equivalent to that of an empire with only one heavily populated city. Come mid to late game, however, this empire will be growing in leaps and bounds faster than the tall empire with few cities. And none of this takes into account other game mechanics that scale exponentially with city number such as trade. So, am I missing something here? Is my math somehow wrong? Is there any reason early on that you would want to be more conservative in the expansion of your empire than the strategy I detailed above? Are there any more conservative strategies (in terms of early expansion) that would theoretically generate equivalent or better results? I can't help but conclude even after this latest patch that rapid expansion is still the best way to go.